Serotonin reuptake transporter

Atomoxetine (Straterra , originally tomoxetine or tomoxetin, 3) was first described and synthesized by chemists at Eli Lilly in the late 1970s and was one of the few compounds that was known to display meaningful selectivity for the norepinephrine reuptake transporter (NET) versus the serotonin reuptake transporter (SERT) and the dopamine reuptake transporter (DAT) (Barnett, 1986 Molloy and Schmiegel, 1997). Atomoxetine was one of several structurally related and commercially successful monoamine reuptake inhibitors that were developed by Lilly for the treatment of various psychiatric disorders (Eig. 17.4). Fluoxetine (43) and duloxetine (44) have both gained approval in the United States as Prozac and Cymbalta , respectively, and nisoxetine (45) is widely used as a tool in biology. 

These drugs increase synaptic serotonin by selectively blocking the serotonin reuptake transporter. In preclinical and human studies acute doses tend to be anxiogenic (Bell and Nutt 1998) but chronic administration has anxiolytic effects, possibly due to downregulation of presynaptic autoreceptors (Blier et al. 1990). There are five SSRIs widely available citalopram, fluoxetine, fluvoxam-ine, paroxetine and sertraline. Escitalopram, the S-enantiomer of citalopram. 

Ranganathan R., E.R. Sawin, C. Trent, and H.R. Horvitz (2001). Mutation in the Caenahab-ditis elegans serotonin reuptake transporter MOD-5 reveal serotonin-dependent and independent activities of fluoxatine. Journal of Neuroscience 21 5871-5884. 

MDR1, multidrug resistance protein-1 MRP1, multidrug resistance-associated protein 1 NET, norepinephrine transporter SERT, serotonin reuptake transporter VMAT, vesicular monoamine transporter. 

NET, norepinephrine reuptake transporter SERT, serotonin reuptake transporter. ... 

CNS, central nervous system GI, gastrointestinal SERT, serotonin reuptake transporter NET norepinephrine reuptake transporter CB, cannabinoid tid, three times daily qd, daily. 

Serotonin reuptake transporter (reduces synaptic serotonin levels)... 

Figure 3.1 How Prozac (fluoxetine) blocks reuptake of serotonin. Normally the serotonin reuptake transporter carries serotonin back into the neuron. Prozac binds to the transporter, causing serotonin to build up outside the neuron.

The new F-labeled phenylthiophenyl derivative, specific for imaging of serotonin reuptake transporters (SERT), was synthesized by F-for-NMe3 substitution and subsequent combined borane and stannous chloride reduction of the nitro and amido group in the precursor (Oya et al. 2002) (O Fig. 42.10e). 

Serotonin, also known as 5-hydroxytryptamine (5-HT) is biosynthesized from tryptophan and is a neurotransmitter. Serotonin plays an important role in many behaviors including sleep, appetite, memory, and mood [52]. People with depressive disorders exhibit low levels of serotonin in the synapses. Protonated serotonin binds to a serotonin reuptake transporter protein, sometimes referred to as the serotonin transporter (SERT) and is then moved to an inward position on the neuron and subsequently released into the cjdoplasm. Selective serotonin reuptake inhibitors (SSRI) bind with high affinity to the serotonin binding site of the transporter. This leads to antidepressant effects by increasing extracellular serotonin levels which in turn enhances serotonin neurotransmission [53]. The SSRI class of antidepressants has fewer side effects than the monoamine oxidase inhibitors. 

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